Synergistic Enteral Regimen for Treatment of the Gangliosidoses

Brief Title

Synergistic Enteral Regimen for Treatment of the Gangliosidoses

Official Title

Synergistic Enteral Regimen for Treatment of the Gangliosidoses (Syner-G)

Brief Summary

      The investigators hypothesize that a combination therapy using miglustat and the ketogenic
      diet for infantile and juvenile patients with gangliosidoses will create a synergy that 1)
      improves overall survival for patients with infantile or juvenile gangliosidoses, and 2)
      improves neurodevelopmental clinical outcomes of therapy, compared to data reported in
      previous natural history studies. The ketogenic diet is indicated for management of seizures
      in patients with seizure disorders. In this study, the ketogenic diet will be used to
      minimize or prevent gastrointestinal side-effects of miglustat. A Sandhoff disease mouse
      study has shown that the ketogenic diet may also improve central nervous system response to
      miglustat therapy (see Denny in "Citations" list below). Patients with infantile and juvenile
      gangliosidoses commonly suffer from seizure disorders, and use of the ketogenic diet in these
      patients may therefore also improve seizure management.

Detailed Description

      The infantile and juvenile forms of GM1 and GM2 gangliosidoses are neurodegenerative
      conditions that are lethal during childhood. There are no known effective therapies available
      for treatment of infantile and juvenile gangliosidoses. Studies of monotherapy with miglustat
      for treatment of these conditions have demonstrated safety, but have not demonstrated notable
      clinical improvement. To date, combination therapy for the infantile and juvenile
      gangliosidoses has not been explored. This study will evaluate a multi-targeted combination
      therapy for treatment of the gangliosidoses, using FDA approved therapies that have
      demonstrated safety in children. It is the aim of this study to learn if combination therapy
      using the "Syner-G" regimen (that is, synergistic enteral regimen for treatment of the
      gangliosidoses) will show improvement in overall survival and clinical benefits in
      neurodevelopmental abilities in children with gangliosidosis diseases.

      This study is planned as a 5-year longitudinal treatment study. Subjects will be started on
      the treatment regimen when they are enrolled in the study. Data will be collected during
      yearly evaluations and at completion of study. Investigators may choose to stop therapy at
      any time, as clinically indicated for individual patients.

      The Ketogenic Diet is a special diet that contains higher amounts of fat and lower amounts of
      carbohydrate compared to an average diet. The purpose of this is to help reduce
      food-miglustat interactions. The ketogenic diet may also help in management of seizures in
      these patients. (The ketogenic diet has been used as an anti-seizure treatment in a variety
      of medical conditions for many decades.) A study in Sandhoff disease mice has shown that the
      ketogenic diet may also help miglustat be more effective in the central nervous system (see
      Denny in "Citations" list below).

      Miglustat will be used to reduce the amount of ganglioside accumulation in the child's cells.
      Miglustat is not FDA approved for treatment of the gangliosidoses. It is FDA approved for a
      different inherited metabolic disease called Gaucher disease type I.

      This study has been issued Investigational New Drug (IND) # 127636 by the U.S. Food and Drug
      Administration (FDA).

Study Phase

Phase 4

Study Type


Primary Outcome

The Duration of Survival of Each Research Subject, Measured in Months and Years

Secondary Outcome

 Rate of Change in Neurocognitive Functioning


GM1 Gangliosidoses



Study Arms / Comparison Groups

 Syner-G Therapy Regimen
Description:  The Syner-G therapy regimen includes switching the research subject to a full-time ketogenic diet, and daily treatment with orally-administered miglustat, for the duration of the 60-month study.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

December 22, 2015

Completion Date

July 31, 2019

Primary Completion Date

July 31, 2019

Eligibility Criteria

        Inclusion Criteria:

          1. Subjects must have a documented infantile or juvenile gangliosidosis disease.

          2. Age: 17 years or less at time of enrollment

          3. Subjects and their caregivers must be willing to work with a ketogenic diet team for
             management of the subject's ketogenic diet.

        Exclusion Criteria:

          1. A desire to not participate

          2. Patients who are older than 17 years will not be enrolled in this study.

          3. Children with severe renal impairment will not be enrolled in this study.

          4. Post-pubertal females who are pregnant, or who are unwilling to use highly-effective
             methods to prevent pregnancy, will be excluded from this study.

          5. Breast-feeding females will be excluded from this study.

          6. Subjects who have an allergy to miglustat or any of the components within the drug
             product will be excluded from this study.




N/A - 204 Months

Accepts Healthy Volunteers



Jeanine R. Jarnes, PharmD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

University of Minnesota


 Rare Diseases Clinical Research Network

Study Sponsor

Jeanine R. Jarnes, PharmD, Principal Investigator, University of Minnesota Fairview Hospital

Verification Date

March 2021